Direct projections from the inferior colliculus drive putative pre-motor sympathetic, respiratory and motor populations in the medulla

We have recently shown that disinhibition of deep layers of the inferior colliculus unmasks coordinated cardiovascular, somatomotor and respiratory responses to multimodal sensory stimuli in the anesthetized rat. As these effects were maintained following extensive decerebration, we proposed that they were mediated by a previously undescribed projection from the inferior colliculus to pontine, brainstem or spinal cardiorespiratory and motor control nuclei. Here we directly examine that hypothesis. Efferent projections from the inferior colliculus were labelled by an AAV vector that drives reporter expression. Three weeks after injection, rats were sacrificed and brains examined for evidence of terminal labelling in regions known to drive sympathetic, respiratory or motor outputs. Injections confined to the region that drives physiological responses resulted in labelling of extensive pontine and medullary projections, with little evidence of projections to the spinal cord or rostral to the hypothalamus. The densest terminal labelling was observed within the rostral ventromedial medulla and Raphe nuclei, and included putative synaptic contacts with spinally projecting neurons. In contrast, no labelling was apparent in other respiratory or cardiovascular control nuclei in the ventrolateral medulla. The functional significance of these projections was confirmed in electrophysiological experiments in vivo, in which stereotypical sympathetic, respiratory and motor responses evoked by disinhibition of the colliculus were blocked by microinjection of GABA agonists in the region of densest terminal labelling. We conclude that a previously undescribed projection from the colliculus to the RVMM/Raphe may drive co-ordinated cardiorespiratory and motor responses to alerting sensory stimuli.